Maternal alcohol and coffee drinking, parental smoking and childhood leukaemia: a French population-based case-control study

We investigated the role of maternal alcohol and coffee drinking during pregnancy and that of parental smoking in the aetiology of childhood leukaemia. A French, population-based, case-control study was conducted, comparing 472 [407 acute lymphoblastic leukaemia (ALL) and 62 acute myeloblastic leukaemia] cases of childhood acute leukaemia (AL) and 567 population controls, frequency-matched with cases on age, gender and region of residence. Both case and control mothers filled in a comprehensive self-administered standardised questionnaire, eliciting detailed data on maternal alcohol and coffee consumption during pregnancy and parental smoking before, during and after pregnancy. Maternal alcohol consumption of more than 1 drink per day was related to ALL (OR = 2.8 [95% CI 1.8, 5.9]). While maternal coffee consumption was not significantly related to AL (OR = 1.4 [95% CI 0.9, 2.3]), highest intake of coffee (more than 3 cups per day) during pregnancy was associated with AL in children whose mothers were non-smokers (OR = 1.9 [95% CI 1.0, 3.5]). No association with parental smoking, either maternal or paternal, was observed with AL. The present results suggest a possible role of the highest consumption of alcohol by the mother during pregnancy in the aetiology of childhood AL.     

Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo

Endometriosis affects 6–10% of women in their reproductive years, causing chronic pelvic pain and infertility. Its pathogenesis remains poorly understood and current treatments, based on hormonal therapy or surgery, are often insufficient. The purpose of our study was to investigate the role of the ERK pathway in the development of endometriosis and to test the effects of protein kinase inhibitors on the proliferation of endometriotic cells in vitro and in vivo. We studied ex vivo human endometrial and endometriotic cells in culture. Stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from patients with endometriosis and from patients without endometriosis. The ERK pathway was explored by western blot on cell lysates and by ELISA on total crushed specimens of endometrium. Cells in culture were treated with A771726, PD98059, and U0126. Human endometriotic lesions were implanted in nude mice. Mice were treated with A771726, leflunomide, PD98059, U0126 or PBS during 2 weeks before sacrifice and extraction of the endometriotic implants for histological examination. We found that the ERK pathway was significantly activated in endometriotic cells and in endometrial cells from patients with endometriosis compared to endometrial cells of control patients, both by ELISA and by western blot. This phenomenon was associated with an increased proliferation of endometriotic cells compared to endometrial cells. Treating endometriotic cells with A771726, PD98059 or U0126 abrogated the phosphorylation of ERK and significantly decreased the cellular proliferation in vitro. In vivo, A771726, leflunomide, PD98059, and U0126 controlled the growth of endometriotic implants in the mouse model of endometriosis. Our study shows that protein kinase inhibitors could be new candidates to treat endometriosis. However, further studies are needed to evaluate their effects and tolerability in humans. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Automated external defibrillator use during cardiopulmonary resuscitation during flight

Automated External Defibrillator (AED) during cardiopulmonary resuscitation should reduce mortality rate after out-of-hospital cardiac arrest. We report a case of defibrillation with AED during flight in a patient suffering cardiac arrest complicating an acute myocardial infarction. Two hours before landing, a 56-years-old man presented sudden cardiac arrest. Flight attendants performed basic cardiac life support, including AED. Five shocks were delivered. After landing, acute myocardial infarction was diagnosed and treated by prehospital thrombolysis and angioplasty with favorable outcome. AED is a crucial link of the chain of survival, especially where advance cardiac live support cannot be performed, like during flight. Despite an increasing AED availability, survival after cardiac arrest during flight remains exceptional.     

Surgical treatment of liver metastasis in patients with colorectal cancer

Half of patients with colorectal cancer have liver metastasis during their illness. Surgical resection of metastases represents the only curative treatment with prolonged survival in more than 50 % of patients. The aim of liver resection is complete excision of the lesions with histological negative margins while preserving sufficient functional liver parenchyma. In patients with diffuse liver disease, the radiofrequency ablation of metastases may be associated with surgical resection. The use of portal vein remobilization and neoadjuvant chemotherapy can also increase the number of patients for curative treatment. Despite this progress, from 50 to 60 % of patients relapse after complete resection of MHCCR. Surgical treatment of recurrent aggressive and effective chemotherapy allows the prolonged survival of these patients. The modern treatment of liver metastasis of colorectal cancers can be envisaged as part of a multidisciplinary approach to increase the number of patients for curative treatment.     

Impact of a Sacrificial Anode as Assessed by Zinc Accumulation in Different Organs of the Oyster <Emphasis Type="Italic">Crassostrea gigas</Emphasis>: Results from Long- and Short-Term Laboratory Tests

Sacrificial anodes made of zinc are currently used in marine environments to mitigate marine corrosion as part of CP systems of immerged metallic structures. The aim of this work was to study zinc bioconcentration in the oyster Crassostrea gigas by performing two in vivo tests during different time periods and at different zinc concentrations. The first test was conducted during a period of 10 weeks at a concentration of 0.53 ± 0.04 mg Zn L⁻¹ to simulate long-term exposure, and a second test was conducted during a 168-hour period at a concentration of 10.2 ± 1.2 mg Zn L⁻¹ to reproduce short-term exposure. In these experiments, the zinc source was an electrochemical device that included a sacrificial anode to mimic the in situ conditions. During the first 14 days of the long-term experiment, digestive glands of C oysters exhibited bioaccumulation of zinc that varied according to the oysters’ reproductive cycle. Both a bioconcentration factor (BCF) of ≤ 13,397 and a zinc accumulation percentage of +297% of zinc occurred in this organ after 10 weeks. The results obtained from the short-term test showed a lower BCF of 405 but a faster bioaccumulation of zinc (starting from the first day) in the same organ. No mortality was observed in long-term assay, but 81.8% of the oysters died at the end of the short-term assay. These results demonstrate the great capacity of C. gigas to accumulate zinc released from the anode, especially when low concentrations are released, as in the case of anode dissolution used as CP. This study confirmed the necessity to monitor this zinc-contamination source in marine environments in relation to the usual oyster consumption by humans (especially in France). No implication for human health of this zinc-contamination source was demonstrated until now, and this was not the purpose of this study; however, zinc remains one of the most abundant nutritionally essential elements in the human body that may affect the human immune system at high-level uptake.     

The mTOR/AKT inhibitor temsirolimus prevents deep infiltrating endometriosis in mice

Deep infiltrating endometriosis (DIE) is a particular clinical and histological entity of endometriosis responsible for chronic pelvic pain and infertility. Here we characterize the proliferative phenotype of DIE cells, to explore the cellular and molecular mechanisms that could explain their aggressive potential. In addition, the inhibition of mTOR/AKT pathway was tested, as a potential treatment of DIE. Included were 22 patients with DIE and 12 control patients without endometriosis. Epithelial and stromal cells were extracted from biopsies of eutopic endometrium and deep infiltrating endometriotic nodules from patients with DIE. Cell proliferation was determined by thymidine incorporation. Oxidative stress was assayed by spectrofluorometry. The ERK and mTOR/AKT pathways were analyzed in vitro by Western blot and for AKT in vivo in a mouse model of DIE. The proliferation rate of eutopic endometrial cells and of deep infiltrating endometriotic cells from DIE patients was higher than that of endometrial cells from controls. The hyperproliferative phenotype of endometriotic cells was associated with an increase in endogenous oxidative stress, and with activation of the ERK and mTOR/AKT pathways. mTOR/AKT inhibition by temsirolimus decreased endometriotic cell proliferation both in vitro and in vivo in a mouse model of DIE. Blocking the mTOR/AKT pathway offers new prospects for the treatment of DIE.     

Laparoscopic Adrenalectomy for Metachronous Metastasis from Renal Cell Carcinoma

BACKGROUND: Metachronous adrenal metastases (AM) from renal cell carcinoma (RCC) are rare. We report our experience of surgical resection in this setting, with particular respect to laparoscopic approach and long-term outcome. METHODS: A retrospective review of 11 patients who underwent adrenalectomy for metachronous AM from RCC was conducted between 2002 and 2005 in a tertiary referral center. RESULTS: CT scan findings were those of an adrenal mass ranging from 2 to 13 cm in diameter with a basal density of 12 to 28 Hounsfield Units and strong heterogeneous enhancement following contrast injection. The surgical procedure consisted of controlateral (n = 5), ipsilateral (n = 2), and bilateral (n = 1) laparoscopic adrenalectomy, whereas three patients underwent controlateral open adrenalectomy for adrenal mass >10 cm. Nine patients were recurrence-free with a median follow-up of 34 months. In the remaining two patients, lung metastases were discovered at postoperative months 28 and 11, respectively. The former patient is alive and free of disease recurrence 32 months after lung metastasis resection, whereas the latter is currently being treated with sunitinib. CONCLUSIONS: This study confirms that prolonged overall and disease free-survival can be achieved in selected patient after laparosocpic adrenalectomy for AM from RCC.     

Antiproliferative effects of cannabinoid agonists on deep infiltrating endometriosis

Deep infiltrating endometriosis (DIE) is characterized by chronic pain, hyperproliferation of endometriotic cells and fibrosis. Since cannabinoids are endowed with antiproliferative and antifibrotic properties, in addition to their psychogenic and analgesic effects, cannabinoid agonists have been evaluated in DIE both in vitro and in vivo. The in vitro effects of the cannabinoid agonist WIN 55212-2 were evaluated on primary endometriotic and endometrial stromal and epithelial cell lines extracted from patients with or without DIE. Cell proliferation was determined by thymidine incorporation and production of reactive oxygen species by spectrofluorometry. ERK and Akt pathways were studied by immunoblotting. Immunoblotting of α-smooth muscle actin was studied as evidence of myofibroblastic transformation. The in vivo effects of WIN 55212-2 were evaluated on Nude mice implanted with human deep infiltrating endometriotic nodules. The in vitro treatment of stromal endometriotic cells by WIN 55212-2 decreased cell proliferation, reactive oxygen species production, and α-smooth muscle actin expression. The decrease in cell proliferation induced by WIN 55212-2 was not associated with a decrease in ERK activation, but was associated with the inhibition of Akt activation. WIN 55212-2 abrogated the growth of endometriotic tissue implanted in Nude mice. Cannabinoid agonists exert anti-proliferative effects on stromal endometriotic cells linked to the inhibition of the Akt pathway. These beneficial effects of cannabinoid agonists on DIE have been confirmed in vivo.